Probiotics as adjunct preventive therapy for childhood diarrhea and antimicrobial resistance in Africa (PRoRota)

Diarrhea is one of the main causes of child deaths globally, killing nearly two million every year. One of the most important causes is the rotavirus. National immunizations have reduced virus-related diarrhea, but vaccine efficacy in Africa remains suboptimal (30-60%) compared to developed nations (80-90%). The efficacy difference could be attributed to various factors, including variation in gut microbiota. 

In low-income countries the intestinal microbiota of children may undergo significant alterations due to several factors, including exposure to faecal contaminated environments, infections caused by pathogens, frequent administration of antibiotics, and malnutrition. Furthermore, the occurrence of environmental enteropathy, which arises from repeated exposure to pathogens, is common. 

Relative abundance of Gram-negative bacteria in the gut microbiome positively correlates with rotavirus vaccine response. Furthermore, use of probiotics is considered an innovative strategy to reduce the intestinal carriage of multidrug-resistant bacteria and may therefore be crucial to raise efficacy of rotavirus vaccine.

In this project we aim to assess the efficacy and safety of using probiotics together with routine rotavirus and other vaccines in reducing diarrheal diseases in infants. 

More specifically we will assess if the adjunct probiotic treatment can:

• Increase immune response to the rotavirus vaccine,
• Reduce incidence of childhood acute diarrhea and improve treatment outcomes,
• Reduce the risk of gut colonization by the multidrug-resistant bacteria.

The project also focuses on: 

• Reducing the costs of probiotic treatment for diarrheal disease versus standard of care,
• Acceptability and feasibility of of using probiotics in infants among key stakeholders,
• Improvement in implementation of hygenic routines for the mothers after receiving WASH education (Water, Sanitation and Hygene),
• Assessing the relationship between changes in climate variables at the inclusion sites in the three countries and the incidence of diarrheal diseases to inform the prediction models for early warning systems.

4000 healthy newborns between 0-3 days of age will be recruited and followed up to 6 months of age. Newborns will receive either a daily multi-strain probiotic supplement or placebo for four weeks. This will be followed by booster doses every four weeks up to 16 weeks of age. The intervention will be administered alongside the standard rotavirus vaccination schedule.

Study will collect dried blood spot samples for analysis of immune reponse to the vaccine, and stool samples for gut microbioma and pathogen analyses.

The study will be implemented in three African countries: Tanzania, Malawi and Ivory Coast.